How Evidence Can Clean the House of Medicine
"Each of us recalls moments when we realized that what we had told our patients, or did for them, was wrong: We had promoted an accepted practice that was, at best, ineffective," Vinayak K. Prasad, MD, MPH, and Adam S. Cifu, MD, wrote in their introduction to Ending Medical Reversal: Improving Outcomes, Saving Lives (Johns Hopkins University Press, 2015). "First there is certainty that a new practice will help extend your life, then there is equal certainty that it does not."
Cifu and Prasad, both practicing physicians at major academic medical centers, have published multiple papers evaluating medical research, including several on medical reversals -- established clinical practices overturned by new or better evidence that reveals harm or at the very least no improvement over the previous standard of care.
And now they present the culmination of 5 years of assessing medical research and subsequent clinical practice alongside potential answers to the question: How can we improve the quality of care we provide and overall patient safety?
To start, each author recounts the medical reversal that humbled him. For Cifu, learning that hormone replacement therapy for postmenopausal women, a treatment he had been initiating every couple of weeks for years "was found to be ineffective or possibly harmful." And for Prasad, that same moment came when a patient died from procedure-related complications with a coronary stent placement that she did not need.
The doctors passionately argue that medical reversal is the most important problem in medicine today, illustrating the impact reversals have had on patient care and the entire healthcare system through clinical practices that have been "adopted without a robust evidence base" -- the breeding ground for medical reversals.
The book highlights vulnerabilities in study designs, questions why subjective outcomes and surrogate outcomes carry the weight they do, and exhibits how the intuitive thinking that leads to practices like nontargeted screening tests and systems interventions in hospitals have resulted in more harm than good.
Twenty-five years after the start of the evidence-based medicine (EBM) movement, clinicians have more research than they know what to do with, but Prasad and Cifu argue that these studies often avoid the big questions in medicine, or that they were built with so much bias, that they are not useful.
The book ends with a clear and thorough proposal for a recalibration throughout healthcare, from medical education and academic medicine career tracks, to clinical trial oversight and retesting of established therapies.
However, the authors carefully note that their intent in compiling this evidence was not to scold or criticize the members of their profession, but to remind clinicians to be humble in their approach to medicine, and to insist on proof before practice.
Watching Medicine Flip-Flop Patient Care
The authors presented a series of case reports that exemplify some of the more severe medical reversals in recent years, and the big trials on which those reversals were based: flecainide therapy for premature ventricular contractions (PVCs), atenolol for hypertension, vertebroplasty for back pain, intensive glucose control for stable type 2 diabetes, and others. And in each case, they homed in on the many factors, weak or flawed research, industry bias, study manipulation, etc., that led to the adoption of these practices.
This approach transitions the narrative into a thoughtful dissection of what they say has been one of the flimsiest benchmarks in medical research -- surrogate end points, a measure, they argue, that has no place in informing clinical practice.
Prasad notes his experience as an oncologist with bevacizumab, a drug that received accelerated approval for the treatment of metastatic breast cancer based on the surrogate end point of progression-free survival despite barely any changes in overall patient survival. (After 3 years, the FDA did reverse the approval.)
Other practices and reversals the authors discuss fall into intuitive logic categories, those things that make sense and should work, but have not been shown to save lives, and in some cases actually caused harm. These included several types of cancer screenings and systems interventions adopted by hospitals like gown-and-glove protocol for inpatients with potential bacterial infections and rapid-response teams.
A Closer Look
The authors spend a substantial amount of time demonstrating how study designs can be manipulated to show favorable outcomes, hide biases, and taint results.
And although all of the medications and devices they discussed were at one time approved by the FDA, Prasad and Cifu were careful to avoid criticizing the agency's actions and regulatory capacity. However, they did point to the ways in which the enforcement of FDA rules has been woefully underachieved.
In the final chapters, Prasad and Cifu argue for changes in most corners of the healthcare system, from the way the next generations of docs could be trained and how academic medical centers should encourage replication research, to placing more of the burden of proof for new therapies on drug makers and eschewing "give it a shot" practices in medicine.
The authors call on their colleagues to test each of the proposals in the book with rigor, and to view their statements not as fundamentalist, but as more of a shift in clinical practice. "As clinicians, we are aware that there needs to be wiggle room -- we will continue to make some decisions without a solid evidence base."
The book ends on a suggestion to make testing clinical practices a widespread and ongoing activity. If a patient has pneumonia and there are two different antibiotics to choose from, ask the patient if they're OK with being enrolled in a clinical trial so the outcome can be tracked.
And with the massive amount of data collected with this process, clinicians could clean "the house of medicine" with a substantial evidence base and to support high-quality healthcare.